Macroporous organosilicon nanocomposites co-deliver Bcl2-converting peptide and chemotherapeutic agent for synergistic treatment against multidrug resistant cancer
| Autor: | Boning Niu, Xiao-kun Zhang, Jingjing Xie, Weixia Xu, Yuehuang Wu |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Drug Cancer Research Dendrimers media_common.quotation_subject Peptide Antineoplastic Agents Nanocomposites 03 medical and health sciences Mice 0302 clinical medicine In vivo Dendrimer Cell Line Tumor Neoplasms medicine Animals Humans Doxorubicin media_common chemistry.chemical_classification Nanocomposite Chemistry Cancer medicine.disease Drug Resistance Multiple 030104 developmental biology Oncology Proto-Oncogene Proteins c-bcl-2 Drug Resistance Neoplasm 030220 oncology & carcinogenesis Cancer cell Cancer research Heterografts Oligopeptides medicine.drug |
| Zdroj: | Cancer letters. 469 |
| ISSN: | 1872-7980 |
| Popis: | Therapeutic biomacromolecules are confronted with in vivo challenges of low bio-stability and poor tumor tissue-penetration. Herein, we report for the first time, our development and characterization of a hybrid nanocomposite for delivering a Bcl-2-converting peptide (NuBCP9, N9 hereafter) and testing its efficacy alone or together with doxorubicin (DOX). The hybrid nanocomposite is composed of the internal large pore sized-mesoporous silica nanoparticles (MSNs) and the external highly-branched polyamidoamine (PAMAM) dendrimers, into which N9 peptide and DOX were encapsulated for the different sub-cellular delivery to treat drug-resistant cancer. The nanocomposite possessed the particle and pore sizes of ~37 nm and ~8 nm, which displayed the superior tumor penetration capacity over naked MSNs both in cultured-3D tumor sphere and in live animal models. Moreover, the dual drug nanocomposite exhibited a great synergistic anticancer effect on Bcl-2-positive cancer cells in vitro and animals with the negligible toxic side effects. The tumor inhibition rate of the nanocomposite (89%) was five times as much as the two drugs combination. This design provides a new effective, safe and versatile strategy to fabricate large pore-sized MSNs with the organic-inorganic hybrid framework to concurrently transport therapeutic peptides and chemotherapeutics to the specific sub-cellular locations for the synergistic cancer therapy and drug resistance reversal, which has significant impact on the development of improved cancer therapeutics. |
| Databáze: | OpenAIRE |
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